Digital microfluidics (DMF) has emerged as a powerful liquid-handling technology for a broad range of miniaturized biological and chemical applications (see, e.g., Jebrail, M. J.; Bartsch, M. S.; Patel, K. D., Digital microfluidics: a versatile tool for applications in Chemistry, biology and medicine. Lab Chip 2012, 12 (14), 2452-2463.). DMF enables real-time, precise, and highly flexible control over multiple samples and reagents, including solids, liquids, and harsh chemicals, without need for pumps, valves, moving parts or cumbersome tubing assemblies. Discrete droplets of nanoliter to microliter volumes are dispensed from reservoirs onto a planar surface coated with a hydrophobic insulator, where they are manipulated (transported, split, merged, mixed) by applying a series of electrical potentials to an embedded array of electrodes. See, for example: Pollack, M. G.; Fair, R. B.; Shenderov, A. D., Electrowetting-based actuation of liquid droplets for microfluidic applications. Appl. Phys. Lett. 2000, 77 (11), 1725-1726; Lee, J.; Moon, H.; Fowler, J.; Schoellhammer, T.; Kim, C. J., Electrowetting and electrowetting-on dielectric for microscale liquid handling. Sens. Actuators A Phys. 2002, 95 (2-3), 259-268; and Wheeler, A. R., Chemistry—Putting electrowetting to work. Science 2008, 322 (5901), 539-540.
This technology allows for high flexibility, facile integration and ultimately cost effective automation of complex tasks.
The present invention relates to the detection of a droplet position and size on a digital microfluidic device. Droplet movement on a DMF device is initiated by the application of high voltage to an electrode pad patterned on an insulating substrate; this step is then repeatedly applied to adjacent electrode pads creating a pathway for a droplet across the device. For better control of the droplet movement, and to ensure a complete droplet translation from one pad to another, feedback systems are often employed to detect the exact position of a droplet upon its actuation. If the droplet has not completed the desired translation, the high voltage could be reapplied.
Most of the feedback/measurement circuits developed to control DMF droplets are based on impedance/capacitance measurements. For example, a system shown in FIGS. 1D and 1E detect droplet position and measure droplet velocity based on impedance measurements (e.g., Shih, S. C. C.; Fobel, R.; Kumar, P.; Wheeler, A. R. A, Feedback Control System for High-Fidelity Digital Microfluidics. Lab Chip 2011 (11), 535-540). The measured values are compared to threshold values to evaluate droplet movement. Velocity of the droplet is calculated based on the length of electrode and the duration of the high voltage pulse. Other examples of capacitance/impedance based systems are used to precisely measure droplet size as it is being dispensed from a reservoir. See, e.g., Ren, H.; Fair, R. B.; Pollack, M. G., Automated on-chip droplet dispensing with volume control by electro-wetting actuation and capacitance metering. Sens. Actuators B 2004 (98), 319; and Gong, J.; Kim, C.-J., All-electronic droplet generation on-chip with real-time feedback control for EWOD digital microfluidics. Lab Chip 2008 (8), 898. In another example, capacitance measurement is used to investigate composition of droplets and mixing efficiency (e.g., Schertzer, M. J.; Ben-Mrad, R.; Sullivan, P. E., Using capacitance measurements in EWOD devices to identify fluid composition and control droplet mixing. Sens. Actuators B 2010 (145), 340).
To obtain feedback signal from a droplet using the prior art systems above, a measuring electrical signal is first supplied to an electrode pad, and then through the top substrate fed to a common measurement circuit. The common circuit provides a single value in each feedback measurement, hence property of a single droplet only (e.g., size, position, composition) can be precisely read in one measurement. Monitoring and control of multiple droplets is not feasible simultaneously but rather in a serial mode.
To provide a solution for real-time monitoring of parallel reactions on DMF devices, we have developed a new electrical feedback system design for the simultaneous detection of multiple droplets and their properties. The properties include but are not limited to droplet position, size, composition, etc. See also, Sadeghi, S.; Ding, H.; Shah, G. J.; Chen, S.; Keng, P. Y.; Kim, C. J.; van Dam, R. M., On Chip Droplet Characterization: A Practical, High-Sensitivity Measurement of Droplet Impedance in Digital Microfluidics. Anal. Chem. 2012 (84), 1915, and Murran M. A.; Najjaran, H., Capacitance-based droplet position estimator for digital microfluidic devices. Lab Chip 2012 (12), 2053.